The Protein Core in the University of Kentucky Center for Molecular Medicine works with biomedical investigators to facilitate the expression, purification, and characterization of recombinant proteins and other macromolecules. It makes available equipment, instrumentation, and expertise not normally be found within individual research laboratories. The Core has fermentors, bioreactors, and tissue culture facilities for expressing recombinant protein in bacteria, yeast, insect, or mammalian cells as required. It also maintains cell cracking equipment and an extensive facility for the purification of recombinant proteins. In addition, a range of analytical instruments for biophysical characterization are available in the Core, including dynamic light scattering, spectropolarimetry, fluorescence, isothermal titration calorimetry, high performance liquid chromatography, analytical ultracentrifugation, and X-ray crystallography. Crystallography facilities include instruments for automated crystallization trials, in house data collection equipment, and membership in a group (SER-CAT) operating a state-of-the-art data collection facility at the Advanced Photon Source located within Argonne National Laboratory. A Core staff member maintains the equipment, provides training and, works with researchers on their individual projects. Experienced users have direct access to Core facilities, while new users are first trained by Core personnel and assisted in initial experiments. Users with more difficult projects receive additional assistance from the Core personnel. Service projects are undertaken selectively for users who lack the expertise or personnel to carry out the work on their own. The Core is used by investigators representing 50-70 research groups each year, with over 4200 individual uses of instruments or facilities documented for the first four years of Phase II COBRE funding. Outreach activities include the Core web site, talks given by Core associated faculty, individual and group training sessions, a monthly research talk series, and participation in graduate courses and an NSF REU summer program. The Core is active in obtaining new instrumentation and introducing new techniques. Transition to a selfsustaining regional facility is planned over the course of Phase III COBRE funding.